Turkiye Klinikleri Journal of Anesthesiology Reanimation

.: ORIGINAL RESEARCH
Effect of Liver Ischemia-Reperfusion Injury on Genotoxicity in Rabbits: Experimental Study
Tavşanlarda Karaciğer İskemi-Reperfüzyon Hasarının Genotoksisite Üzerine Etkisi: Deneysel Çalışma
Meltem BEKTAŞa , Ela KADIOĞLUa , Mert NAKİPb , Mehmet ÇAKIRCAa , Ayşe ÖZCANc , Çetin KAYMAKc
aDepartment of Anesthesiology and Reanimation, Health Sciences University Ankara Training and Research Hospital, Ankara, Türkiye
bDepartment of Toxicology, Gazi University Faculty of Pharmacy, Ankara, Türkiye
cDepartment of Anesthesiology and Reanimation, Health Sciences University Ankara Health Application and Research Center, Ankara, Türkiye
Turkiye Klinikleri J Anest Reanim. 2023;21(2):47-52
doi: 10.5336/anesthe.2023-96522
Article Language: EN
Full Text
ABSTRACT
 Objective: Ischemia-reperfusion (I-R) injury is defined as the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow to ischemic tissues. In our study, it was aimed to examine the potential DNA injury effects of liver IR injury with an experimental animal model. Material and Methods: In the study, modeling was done with seven male New Zealand rabbits. Blood samples were taken before the experimental IR model, 30 minutes after ischemia, and 60 minutes after reperfusion. The DNA damage in the blood of the rabbits was measured using Tail Length, Intensity, and Moment techniques. Statistical significance was determined using one-way analysis of variance (ANOVA) and Tukey's post hoc test. Results: There are significant differences between control-ischemia, control-reperfusion and I-R groups in all 3 measurements. Tail length; increased by 51.84%, 54.16% after ischemia and reperfusion, respectively. Tail length increased by 134.09% between control and reperfusion. Similarly, tail density and tail moment were increased by 78.95% (after ischemia), 77.96% (after reperfusion), 85.54% (after ischemia), 165.52% (after reperfusion) respectively. Conclusion: Tissue blood flow disruption is known to occur tissue hypoxia that triggers anaerobic respiration. Restoring blood flow to a hypoxic-tissue results in an increase in reactive oxygen species production. Literature stated I/R-related DNA damage may result from the formation of oxygen radicals during the reperfusion period. Moreover, it induces oxidative damage and exceeds the antioxidative capacity of circulating leukocytes, leading to DNA damage. In our study, DNA lesions characteristic of DNA damage mediated by free radicals were detected at a significantly increased level during reperfusion.

Keywords: Comet assay; DNA damage; ischemia; reperfusion injury; rabbits
ÖZET
 Amaç: İskemi-reperfüzyon (I-R) hasarı, iskemik dokulara kan akışının yeniden sağlanmasını takiben, hücresel işlev bozukluğunun ve ölümün paradoksal alevlenmesi olarak tanımlanır. Çalışmamızda, deneysel hayvan modeli ile karaciğer I-R hasarının potansiyel DNA hasarı etkilerinin incelenmesi amaçlanmıştır. Gereç ve Yöntemler: Çalışmada, 7 adet erkek Yeni Zelanda tavşanı ile modelleme yapılmıştır. Deneysel I-R modeli öncesi, iskemi sonrası 30. dk ve reperfüzyon sağlandıktan 60 dk sonra kan örnekleri alınmıştır. Tavşanların kanlarındaki DNA hasarı Kuyruk Uzunluğu, Yoğunluk ve Moment teknikleri kullanılarak ölçüldü. İstatistiksel anlamlılık, tek yönlü varyans analizi (ANOVA) ve Tukey'in post hoc testi kullanılarak belirlendi. Bulgular: Her 3 ölçümde hem kontrol-iskemi hem kontrol-reperfüzyon hem de I/R grupları arasında anlamlı farklılıklar vardır. Kuyruk uzunluğu; iskemi ve reperfüzyon sonrasında sırasıyla %51,84 ve %54,16 artmıştır. Kuyruk uzunluğu, kontrol ve reperfüzyon arasında %134,09 artmıştır. Benzer şekilde, kuyruk yoğunluğu ve kuyruk momenti iskemi ve reperfüzyon sonrası sırasıyla %78,95 (iskemi sonrası), %77,96 (reperfüzyon sonrası) ve %85,54 (iskemi sonrası), %165,52 (reperfüzyon sonrası) artış göstermiştir. Sonuç: Doku kan akımının bozulmasının anaerobik solunumu tetikleyen doku hipoksisi oluşturduğu bilinmektedir. Hipoksik bir dokuya kan akışının yeniden sağlanması reaktif oksijen türlerinin üretiminde artışa neden olur. Literatürde, I-R ile ilişkili DNA hasarı, reperfüzyon periyodu sırasında oksijen radikallerinin oluşumundan kaynaklanabilir. Ayrıca oksidatif hasara neden olur ve dolaşımdaki lökositlerin antioksidan kapasitesini aşarak DNA hasarına yol açar. Çalışmamızda, serbest radikallerin aracılık ettiği DNA hasarının özelliği olan DNA lezyonlarının, reperfüzyon sırasında önemli ölçüde arttığı tespit edilmiştir.

Anahtar Kelimeler: Comet assay; DNA hasarı; iskemi; reperfüzyon hasarı; tavşanlar
REFERENCES:
  1. Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW, et al. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem. 2018;46(4):1650-67. [Crossref]  [PubMed] 
  2. Wang HB, Yang J, Ding JW, Chen LH, Li S, Liu XW, et al. RNAi-mediated down-regulation of CD47 protects against ischemia/reperfusion-induced myocardial damage via activation of eNOS in a rat model. Cell Physiol Biochem. 2016;40(5):1163-74. [Crossref]  [PubMed] 
  3. Liao W, McNutt MA, Zhu WG. The comet assay: a sensitive method for detecting DNA damage in individual cells. Methods. 2009;48(1):46-53. [Crossref]  [PubMed] 
  4. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 2004;26(3):249-61. [Crossref]  [PubMed] 
  5. Panda SK, Ravindran B. Isolation of human PBMCs. Bio-Protocol. 2013;3(3):e323. [Crossref] 
  6. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175(1):184-91. [Crossref]  [PubMed] 
  7. Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med. 2007;42(2):153-64. [Crossref]  [PubMed] 
  8. de Jong HK, van der Poll T, Wiersinga WJ. The systemic pro-inflammatory response in sepsis. J Innate Immun. 2010;2(5):422-30. [Crossref]  [PubMed] 
  9. Terada LS, Willingham IR, Rosandich ME, Leff JA, Kindt GW, Repine JE. Generation of superoxide anion by brain endothelial cell xanthine oxidase. J Cell Physiol. 1991;148(2):191-6. [Crossref]  [PubMed] 
  10. Ichikawa H, Flores S, Kvietys PR, Wolf RE, Yoshikawa T, Granger DN, et al. Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells. Circ Res. 1997;81(6):922-31. [Crossref]  [PubMed] 
  11. Inauen W, Payne DK, Kvietys PR, Granger DN. Hypoxia/reoxygenation increases the permeability of endothelial cell monolayers: role of oxygen radicals. Free Radic Biol Med. 1990;9(3):219-23. [Crossref]  [PubMed] 
  12. Yin J, Luo XG, Yu WJ, Liao JY, Shen YJ, Zhang ZW. Antisense oligodeoxynucleotide against tissue factor inhibits human umbilical vein endothelial cells injury induced by anoxia-reoxygenation. Cell Physiol Biochem. 2010;25(4-5):477-90. [Crossref]  [PubMed] 
  13. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190(3):255-66. [Crossref]  [PubMed] 
  14. McLeod LL, Alayash AI. Detection of a ferrylhemoglobin intermediate in an endothelial cell model after hypoxia-reoxygenation. Am J Physiol. 1999;277(1):H92-9. [Crossref]  [PubMed] 
  15. He F, Li J, Liu Z, Chuang CC, Yang W, Zuo L. Redox mechanism of reactive oxygen species in exercise. Front Physiol. 2016;7:486. [Crossref]  [PubMed]  [PMC] 
  16. Babior BM. Phagocytes and oxidative stress. Am J Med. 2000;109(1):33-44. [Crossref]  [PubMed] 
  17. Stadtman ER, Levine RL. Protein oxidation. Ann N Y Acad Sci. 2000;899:191-208. [Crossref]  [PubMed] 
  18. Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000;21(3):361-70. [Crossref]  [PubMed] 
  19. Ghosh R, Mitchell DL. Effect of oxidative DNA damage in promoter elements on transcription factor binding. Nucleic Acids Res. 1999;27(15):3213-8. [Crossref]  [PubMed]  [PMC] 
  20. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000;279(6):L1005-28. [Crossref]  [PubMed] 
  21. Nguyen T, Yang CS, Pickett CB. The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress. Free Radic Biol Med. 2004;37(4):433-41. [Crossref]  [PubMed] 
  22. Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD, et al. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 2005;1(6):401-8. [Crossref]  [PubMed] 
  23. Nakamura H, Nakamura K, Yodoi J. Redox regulation of cellular activation. Annu Rev Immunol. 1997;15:351-69. [Crossref]  [PubMed] 
  24. Biolo G, Antonione R, De Cicco M. Glutathione metabolism in sepsis. Crit Care Med. 2007;35(9 Suppl):S591-5. [Crossref]  [PubMed] 
  25. Droy-Lefaix MT, Drouet Y, Geraud G, Hosford D, Braquet P. Superoxide dismutase (SOD) and the PAF-antagonist (BN 52021) reduce small intestinal damage induced by ischemia-reperfusion. Free Radic Res Commun. 1991;12-13 Pt 2:725-35. [Crossref]  [PubMed] 
  26. Fantone JC, Ward PA. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol. 1982;107(3):395-418. [PubMed]  [PMC] 
  27. Dix TA, Hess KM, Medina MA, Sullivan RW, Tilly SL, Webb TL. Mechanism of site-selective DNA nicking by the hydrodioxyl (perhydroxyl) radical. Biochemistry. 1996;35(14):4578-83. [Crossref]  [PubMed] 
  28. Salvemini D, Wang ZQ, Zweier JL, Samouilov A, Macarthur H, Misko TP, et al. A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science. 1999;286(5438):304-6. [Crossref]  [PubMed] 
  29. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990;87(4):1620-4. [Crossref]  [PubMed]  [PMC] 
  30. Salvemini D, Wang ZQ, Stern MK, Currie MG, Misko TP. Peroxynitrite decomposition catalysts: therapeutics for peroxynitrite-mediated pathology. Proc Natl Acad Sci U S A. 1998;95(5):2659-63. [Crossref]  [PubMed]  [PMC] 
  31. Tang D, Kang R, Zeh HJ 3rd, Lotze MT. High-mobility group box 1, oxidative stress, and disease. Antioxid Redox Signal. 2011;14(7):1315-35. [Crossref]  [PubMed]  [PMC] 
  32. Li J, Kokkola R, Tabibzadeh S, Yang R, Ochani M, Qiang X, et al. Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol Med. 2003;9(1-2):37-45. [Crossref]  [PubMed]  [PMC] 
  33. Granger DN, Kvietys PR. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol. 2015;6:524-51. [Crossref]  [PubMed]  [PMC] 

.: Up To Date

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com